Nmda antagonists: their role in neuroprotection

International Review of Neurobiology

Volumn , Issue 40, 1996, Pages 137-171

  Small, Daniel L ^a   Buchan, Alastair M ^b  

^a NATIONAL RESEARCH COUNCIL CANADA   (Canada)

^b UNIVERSITY OF CALGARY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N METHYLASPARTIC ACID; NEUROPROTECTIVE AGENT;

ANIMAL; BRAIN ISCHEMIA; CELL CULTURE; DISEASE MODEL; DRUG ANTAGONISM; DRUG EFFECT; HUMAN; METABOLISM; NERVE CELL; PATHOLOGY; PHYSIOLOGY; REVIEW;

ANIMALS; BRAIN ISCHEMIA; CELLS, CULTURED; DISEASE MODELS, ANIMAL; HUMANS; N-METHYLASPARTATE; NEURONS; NEUROPROTECTIVE AGENTS; RECEPTORS, N-METHYL-D-ASPARTATE;

EID: 33845189959     PISSN: 00747742     EISSN: None     Source Type: Book Series    
DOI: 10.1016/s0074-7742(08)60719-9     Document Type: Article

References (229)

1. Aitken, P.G., Balestrino, M. & Somjen, G.G. (1988) NMDA antagonists: lack of protective effect against hypoxic damage in CA1 region of hippocampal slices, iïeurosci. Letts. 89, 187-192.
2. Aitken, EG. & SchifT, SJ. (1986) Selective neuronal vulnerability to hypoxia in vitro. Neurosci. Letts. 67, 92-96.
3. Anantharam, V, Panchal, R.G., \Vilson, A., Kolchine, V.V., Treistman, S.N. & Bayley, H. (1992) Combinatorial RNA splicing alters the surface charge on the NMDA receptor. FEBS Letts. 305, 27-30.
4. Anegawa, NJ., Lynch, D.R., Verdoorn, T.A. & Pritchett, D.B. ( 1995) Transfection of N-methyl-D-aspartate receptors in a non-neuronal cell line leads to cell death. J. Neumchem. 64, 2004-2012.
5. Armstrong, D.L. (1991) The hippocampal tissue slice in animal models of CNS disorders. j\eunsd. Behav. Rev. 15, 79-83.
6. Aronowski, J., Waxham, M.N. & Grotta, J.C. (1993) Neuronal protection and preservation of calcium/calmodulin-dependent protein kinase II and protein kinase G activity by dextrorphan treatment in global ischaemia.J. Cereb. Blood Flow Afetab. 13, 550-557.
7. Ascher, P. & Johnson, J.W. (1994) The NMDA receptor, its channel, and its modulation by glycine. In TheMlDA Receptor, 2nd edn (eds Collingridge, G.L. & \Vatkins, J.C.). New York, Oxford University Press, pp. 177-205.
8. Bennan, P.E., Graham, D.I., Lees, K.R. & McCulloch, J. (1994) Neuroprotective effect of remacemide hydrochloride in focal cerebral ischaemia in the cat. Brain Res. 664, 271-275.
9. Béhé, P. Stern, P., \Vyllie, DJ.A., Nassar, M., Schocpfer, R. & Colquhoun, D. (1995) Determination of NMDA NR1 subunit copy number in recombinant NMDA receptors. Proc. R. Soc. Lend. B. 262, 205-213.
10. Beneviste, H., Drejer.J., Schousboe, A. & Diemer, N.H. (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischaemia monitored by intracerebral microdialysis. J. jVeurochem. 43, 1369-1374.
11. Bennett,J.A. & Dingledine, R. (1995) Topology profile for a glutamate receptor: Three transmembrane domains and a channel-linking re-entrant membrane loop. Neuron 14, 373-384.
12. Bidder, P.E. & Hansen, B.M. (1994) Causes of calcium accumulation in rat cortical brain slices during hypoxia and ischaemia: role of ion channels and membrane damage. Brain fies. 665, 269-276.
13. Bielenberg, G.W. & Beck, T. (1991) The effects ofdizocilpine (MK-801), phencyclidine, and nimodipine on infarct size 48 h after middle cerebral artery occlusion in the rat. Brain Res. 552, 338-342.
14. Block, G.A. & Pulsinelli, W.A. (1987) N-methyl-D-aspartate antagonists: failure to prevent ischaemia-induced selective neuronal damage. In Cerebroi'oscular Diseases (eds Raichle, M.E. & Powers, \VJ.), pp. 3742. Raven Press, New York.
15. Boast, C.A. (1988) Neuroprotection after brain ischaemia: role of competitive M-methyl-Daspartate antagonists. In Frontiers in Excitatory Amino Acid Research (ed. Liss, A.R.), pp. 691-698. A.R. Liss Inc., New York.
16. Boast, C.A., Gerhardt, S.C., Pastor, G., LehmannJ., Etienne, P.E. & LiebmanJ.M. (1988) The N-methyl-D-aspartate antagonists CGS 19755 and CPP reduce ischaemic brain damage in gerbils. Brain Res. 442, 345-348.
17. Boje, K.M., Skolnick, P., Raber, J., Fletcher, R.T. & Chader, G. (1992) Strychnine-insensitive glycine receptors in embryonic chick retina: characteristics and modulation of NMDA of neurotoxicity. jMeurochem. Int. 20, 473-480.
18. Boje, K.M., Wong, G. & Skolnick, P. (1993) Desensitization of the NMDA receptor complex by glycinergic ligands in cerebral granule cell cultures. Brain Res. 603, 207-216.
19. Bowe, M.A. & Nadler, J.V (1990) Developmental increase in the sensitivity to magnesium of NMDA receptors on CA1 hippocampal pyramidal cells. Dei: Brain Res. 56, 55-61.
20. Bruno, VM.G., Goldberg, M.P., Dugan, L.L., Giffard, R.G. & Choi, D.W. (1994) Neuroprotective effect of hypothermia in cortical cultures exposed to oxygen-glucose deprivation or excitatory amino acids. J. J Neurochem. 63, 1398-1406.
21. Buchan, A.M. (1990) Do NMDA antagonists protect against cerebral ischaemia: Are clinical trials warranted? Cmbrorasc. Brain Metab. Rev. 2, 1-26.
22. 2+-channel blocker prevents CA1 injury 24 hr following severe forebrain ischaemia and reduces infarction following focal ischaemia. J. Cereb. Blood How Metab. 14,903-914.
23. Buchan, A.M. & Pulsinelli, W.A. (1990) Hypothermia but not the N-methyl-D-aspartate antagonist, MK-801, attenuates neuronal damage in gerbils subjected to transient global ischaemia. J.Neurosci. 10, 311-316.
24. Buchan, A.M., Slivka, A. & Xue, D. (1992) The effect of the NMDA receptor antagonist MK801 on cerebral blood flow and infarct volume in experimental focal stroke. Brain Res. 574, 171-177.
25. Buchs, P.A., Stoppini, L. & Muller, D. (1993) Structural modifications associated with synaptic development in area C A1 of rat hippocampal organotypic cultures. Dei: Brain Res. 71,81-91.
26. Buller, A.L., Larson, H.C., Schneider, B.E., Beaton, J.A., Morrisett, R.A. & Monaghan, D.T. (1994) The molecular basis of NMDA receptor subtypes: Native receptor diversity is predicted by subunit composition. J. j\eurosd. 14, 5471-5484.
27. Bulloch, R., Graham, D.I., Chen, M.H., Low, D. & McCulloch, J. (1990a) Focal cerebral ischaemia in the cat: pretreatment with a competitive NMDA receptor antagonist, D-CPPene. J. Cereb. Blood Flow Metab. 10, 668-674.
28. Bulloch, R., McCulloch, J., Graham, D.I., Lowe, D., Chen, M.H. & Teasdale, G.M. (1990b) Focal ischaemic damage is reduced by CPPene studies in two animal models. Stroke 21, III32-III36.
29. Burnashev, N., Monyer, H., Seebcrg, P.H. & Sakmann, B. (1992a) Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron 8, 189-198.
30. Burnashev, N., Schoepfer, R., Monyer, H., Ruppersberg, J.P., Günther, W, Seeberg, P. & Sakmann, B. (1992b) Control by asparagine residues of calcium permeability and magnesium blockade in the NMDA receptor. Scimce 257, 1415-1419.
31. Caeser, M. & Aertsen, A. ( 1991 ) lorphological organization of rat hippocampal slice cultures. J. Comp.j\euwl. 307, 87-106.
32. Carter, C., Benavides,J., Legendre, P., VincentJ.D., Noel, F., Thuret, F., Lloyd, K.G., Arbilla, S., Zivkovic, B., MacKenzie, E.T., Scatton, B. & Langer, S.Z. (1988) Ifenprodil and SL 82.0715 as cerebral antiischaemic agents. II. Evidence for jY-methyl-D-aspartate receptor antagonist properties. J. Pharmacol. Exp. Ther. 247, 1222-1232.
33. 2+ block of NMDA receptor channels as a mechanism of modulation. Nature 356, 521-523.
34. Chen, H.S.V, Pelligrini, J.W., Agganvai, S.K., Lei, S.Z., Warach, S.,Jensen, F.E. & Lipton, S.A. (1992) Open channel block of N-methyl-D-aspartate (NMDA) responses by memantine: Therapeutic advantage against NMDA receptor-mediated neurotoxicity. J. jYatrosci. 12, 4427-4436.
35. Choi, D.W., Koh,J.Y. & Peters, S. (1988) Pharmacology of glutamate neurotoxicity in cortical cell culture: Attenuation by NMDA antagonists. J. Neurosd. 8, 185-196.
36. Choi, D.W., Maulucci-Gedde, M. & Kriegstein, A.R. (1987) Glutamate neurotoxicity in cortical cell culture. J. Neumti. 7, 357-368.
37. Clark, G.D. & Rothman, S.M. (1987) Blockade of excitatory amino acid receptors protects anoxic hippocampal slices. Neurosci. 21, 665-671.
38. Coyle, J.T. (1983) Neurotoxic action of kainic acid. J. jVeurockem. 41, 1-11.
39. Curtis, D.R. & Johnston, G.A.R. (1974) Amino acid transmitters in the mammalian CNS. Ergebnisse der Physiologie 69, 97-188.
40. Dezsi, L., Greenberg, J.H., Sladky.J., Araki, N., Hamar.J. & Reivich, M. (1994) Prolonged effects of MK-801 in the cat during focal cerebral ischaemia and recovery: survival, EEG activity and histopathology. J.Xeurol. Sei. 121, 110-120.
41. Didier, M., Xu, M., Berman, S.A. & Bursztajn, S. (1995) Differential expression and coassembly of NMDAzl and e subunits in the mouse cerebellum during postnatal development. XeuroReport 6, 2255-2259.
42. Donevan, S.D. & Rogawski, M.A. (1993) GYKI 52466, a 2,3-benzodiazepine, is a highly selective, noncompetitive antagonist of AMPA/kainate receptor responses. Neuron 10, 51-59.
43. Durand, G.M., Bennett, M.VL. & Zukin, R.S. (1993) Splice variants of the N-methyl-D-aspartate receptor NR1 identify domains involved in regulation by polyamines and protein kinase C. Proc. NatlAcad. Sei. USA 90, 6731-6735.
44. Durand, G.M., Gregor, P., Zheng, X., Bennett, M.VL., Uhl, G.R. & Zukin, R.S. (1992) Cloning of an apparent splice variant of the rat N-methyl-D-aspartate receptor NMDAR1 with altered sensitivity to polyamines and activators of protein kinase C. Proc. j\all Acad. Sei. USA 89, 9359-9363.
45. Durkin, J.P., Tremblay, R., Buchan, A., Blosser, J., Chakravarthy, B., Mealing, G. & Song, D. (1996) An early loss in membrane protein kinase C activity precedes the excitatory amino acid-induced death of primary cortical cultures.,/ j\eurochem. 66, pp. 951-962.
46. Duverger, D. & MacKenzie, E.T. (1988) The quantification of cerebral infarction following focal ischaemia in the rat: influence of strain, arterial pressure, blood glucose concentration, and age. J. Cereb. Blood Flow Metab. 8, 449-461.
47. Dux, E., Oschlies, U., \Viessner, C. & Hossmann, K.-A. (1992) Glutamate-induced ribosomal disaggregation and ultrastructural changes in rat cortical neuronal culture. Protective effect of horse serum. Neurosci. Letts. 141, 173-176.
48. Eimeri, S. & Schramm, M. (1991 a) Acute glutamate toxicity in cultured cerebellar granule cells: Agonist potency, effects ofpH, Zn2+ and the potentiation by serum albumin. Brain Res. 560, 282-290.
49. Eimeri, S. & Schramm, M. (1991b) Acute glutamate toxicity and its potentiation by serum albumin are determined by the Ca2+ concentration. Neurosci. Letts. 130, 125-127.
50. Erdö, S.L., Michler, A., WoIffJ.R. & Tytko, H. (1990) Lack of excitatoxic cell death in serum-free cultures of rat cerebral cortex. Brain Res. 526, 328-332.
51. Erdö, S.L. & Schafer, M. (1991) Memantine is highly potent in protecting cortical cultures against excitotoxic cell death evoked by glutamate and JV-methyl-D-aspartate. Em. J. Pharmacol 198, 215-217.
52. Favaron, M., Manev, H., Alho, H., Bertolino, M., Ferret, B., Guidotti, A. & Costa, E. (1988) Gangliosides prevent glutamate and kainate neurotoxicity in primary neuronal cultures of neonatal rat cerebellum and cortex. Proc. NallAcad. Sei. USA 85, 7351-7355.
53. Favit, A., Nicoletti, E, Scapagnini, U. & Canonico, P.L. (1992) Ubiquinone protects cultured neurones against spontaneous and excitotoxin-induced degeneration. J. Cereb. Blood Flow Melab. 12, 638-645.
54. Feldman, E., Gordon, N., Brooks, J.M., Brass, L.M., Fayad, P.B., Sawaya, K.L., Nazareno, E & Levine, S.R. (1993) Factors associated with early presentation of acute stroke. Stroke 24, 1805-1810.
55. Felipo, V, Miiiana, M.D. & Grisola, S. (1993) Inhibitors of protein kinase C prevent the toxic-ity of glutamate in primary neuronal cultures. Brain Res. 604, 192-196.
56. Ferkany, J.W., Kyle, DJ., \VUlets, J., Rzeszotarski, WJ., Guzewska, M.E., Ellenbergcr, S.R., Jones, S.M., Sacaan, A.I., Snell, I.D., Borosky, S.,Jones, B.E.,Johnson, K.M., Balster, R.L., Burchett, K., Kawasaki, K., Hoch, D.B. & Dingledine, R. (1989) Pharmacological profile of NPC 12626, a novel, competitive N-methyl-D-aspartate receptor antagonist. J. Pharmacol. Exp. Ther. 250, 100-109.
57. Fisher, M., Jones, S. & Sacco, R.L. (1994) Prophylactic neuroprotection for cerebral ischaemia. Stroke 25, 1075-1080.
58. Fleischer, J.E., Tateishi, A., Drummond, J.G., Scheller, M.S., Grafe, M.R., Zornow, M.H., Shearman, G.T. & Shipiro, H.M. (1989) MK-801, an excitatory amino acid antagonist, does not improve neurologic outcome follo\ving cardiac arrest in cats. J. Cereb. Blood Flow Aletab. 9, 795-804.
59. Foster, A.C., Gill, R., KempJ.A. & Woodruff, G.N. (1987) Systemic administration of MK-801 prevents.A-methyl-D-aspartate-induced neuronal degeneration in rat brain. Neurosci. Letts. 76, 307-311.
60. France, C.P., Wood, J.H. & Ornstein, P. (1989) The competitive N-methyl-D-aspartate (NMDA) antagonist CGS 19755 attenuates the rate-decreasing effects of NMDA in rhesus monkeys without producing ketamine-like discriminative stimulus effects. Eut J. Pharmacol. 159, 133-139.
61. Gähwiler, B.H. (1981) Organotypic monolayer cultures of nervous tissue.J. Neurosci. Meth. 4, 329-342.
62. Gähwiler, B.H. (1988) Organotypic cultures of neural tissue. Trends. Jfeurosci. 11, 484-189.
63. Gamzu, E.R. & McBurney, R. (1994) Cerestat711 (CNS1102)-preliminary results in stroke and TBI patients. Neuropychoparmacology. 10, S592.
64. Germano, I.M., Pitts, L.H., Meldrum, B.S., Bartkowski, H.M. & Simon, R.P. (1987) Kynurenate inhibition of cell excitation decreases stroke size. Ann. Neural. 22, 730-734.
65. Gidh-Jain, M., Huang, B.Jain, P., Battula, V. & El-Sherif, N. (1995) Reemergence of the fetal pattern of L-type calcium channel gene expression in non-infarcted myocardium during left ventricular remodeling. Biochem. Biopfys. Res. Comm. 216, 892-897.
66. Gill, R., Foster, A.C. & Woodruff, G.N. (1987) Systemic administration of MK-801 protects against ischaemia-induced hippocampal neurodegeneration in the gerbil. J. Neurosd. 7, 3343-3349.
67. Gill, R., Foster, A.C. & Woodruff, G.N. (1988) MK-801 is neuroprotective in gerbils when administered during the post-ischaemic period. Neurosdence 25, 847-855.
68. Gill, R., Hargreaves, RJ. & Kemp, J.A. (1995) The neuroprotective effect of the glycine site antagonist 3-(+)-of-4-methyl-HA966 (L-687 414) in a rat model offocal ischaemia. J. Cereb. Blood Flow Melab. 15, 197-204.
69. Ginsberg, M.D. & Busto, R. (1989) Rodent models of cerebral ischaemia. Stroke 20, 1627-1642.
70. Goldberg, M.P., Pham, P.C. & Choi, D.W. (1987a) Dextrorphan and dextromethorphan attenuates hypoxic injury in neuronal culture. Neurosci. Letts. 80, 11-15.
71. Goldberg, M.P., Weiss.J.H., Pham, P.C. & Choi, DAY. (1987b) N-methyl-D-aspartate receptors mediate hypoxic neuronal injury in cortical culture. J. Pharmacol. Exp. TTierap. 243, 784-791.
72. Gotti, B., Benavides, J., MacKenzie, E.T. & Scatton, B. (1990) The phamacotherapy offocal cortical ischaemia in the mouse. Brain Res. 522, 290-301.
73. Gotti, B., Duverger, D., Burtin, D., Carter, C., Dupont, R., Frost, J., Gaudilliere, B., MacKenzie, E.T., Rousseau, J. & Scatton, B. (1988) Ifenprodil and SL 882.0715 as cerebral anti-ischaemic agents. I. Evidence for efficacy in models of focal cerebral ischaemia. J. Pharmacol. Exp. Ther. 247, 1211-1221.
74. Grotta, J.C., Picone, C.M., Ostrow, P.T., Strong, R.A., Earls, R.M., Yao, L.P., Rhoades, H.M. & Dedman, J.R. (1990) CGS-19755, a competitive NMDA receptor antagonist, reduces calcium-calmodulin binding and improves outcome after global cerebral ischaemia. Ann. Neurol. 27, 612-619.
75. Hartley, D.M., Kurth, M.C., Bjerkness, L., Weiss, J.H. & Choi, D.W. (1993) Glutamate receptor-induced 4oCa2+ accumulation in cortical cell culture correlates with subsequent neuronal degeneration. J.Neuwsci. 13, 1993-2000.
76. Hartmann, H.A., Kirsch, G.E., Drewe, J.A., Tagliatela, M., Joho, R.H. & Brown, A.M. (1991) Exchange of conduction pathways between two related K+ channels. Science 251, 942-944.
77. Hasegawa, Y, Fisher, M., Baron, B.M. & Metcalf, G. (1994) The competitive NDA antagonist MDL-100 453 reduces infarct size after experimental stroke. Stroke 25, 967-973.
78. Herrling, P.L. (1994) D-CPPene (SDZ EAA 494), a competitive NMDA antagonist: results from animal models and first results in humans. Neuropharmacology 10, S591.
79. Heurteux, C., Lauritzen, I., Widmann, C. & Lazdunski, M. (1994) Glutamate-induced overexpression of NMDA receptor messenger RNAs and protein triggered by activation of AMPA/kainate receptors in rat hippocampus follo\ving forebrain ischaemia. Brain Res. 659, 67-74.
80. Hollmann, M., BoulterJ., Maron, C., Beasley, L., SulivanJ., Pecht, G. & Heinemann, S. (1993) Zinc potentiates agonist-induced currents at certain splice variants of the NMDA receptor. Neuron 10, 943-954.
81. Hossman, K.A. (1994) Glutamate-mediated injury in focal cerebral ischaemia: The excitotoxin hypothesis revisited. Brain Pathol. 4, 23-36.
82. Hossman, K. & Kleihues, P. (1973) Reversibility of ischaemic brain damage. Arch. Neural. 29, 375-384.
83. Inglefield, J.R., Wilson, C.A., Barrier, A.E., Chase, PJ., Jones, K.S. & Schwanz, R.D. (1995) Post-ischaemic changes in GABAA receptor al subunit expression in CA1 hippocampus: Reversal by diazepam. Sac. Neurosci. Abstr. 21, 393.14.
84. Izumo, S., Lompre, A.M., Matsuoka, R., Koren, G., Schwartz, K., Nadal-Ginard, B. & Mahdavi, V (1987) Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy: Interactions between hemodynamic and thyroid hormoneinduced signals. J. Clin. Incest. 79, 970-977.
85. Jensen, M.I. & Auer, R.N. (1988) Ketamine fails to protect against ischaemic neuronal necrosis in the rat. Br. J. Anaesth. 61, 206-210.
86. Jensen, M.L. & Auer, R.N. (1989) Intraventricular infusion of 2-amino-7-phosphonoheptanoate (APH) mitigates ischaemic brain damage. Neural. Res. 11, 37-10.
87. Johansen, F.F.,Jorgensen, M.B. & Diemer, N.H. (1986) Ischaemic CA-1 yramidal cell loss is prevented by preischaemic colchicine destruction of dentate gyrus granule cells. Brain Res. 377, 344-347.
88. 2+ of N-methylD-aspartate-activated channels. Bioplys.J. 57, 1085-1090.
89. Jones, S.M. & Rogawski, M.A. (1992) The anticonvulsant (±)-5-aminocarbonyl-10,11-dihydro5//-dibenzo [a,d] cyclohepten-5,10-imine (ADCI) selectively blocks NMDA-activated current in cultured rat hippocampal neurones: kinetic analysis and comparison with dizocilpine. Mol. Neuropharmacolgy. 2, 303-310.
90. Jorgensen, M.B., Johansen, F.F. & Diemer, N.H. (1987) Removal of the entorhinal cortex protects hippocampal CA-1 neurones from ischaemic damage. Ada Jfeuropathol. 73, 189-194.
91. Kaku, C.A., Giffard, R.G. & Choi, D.W. (1993) Neuroprotective effects of glutamate antagonists and extracellular acidity. Science 260, 1516-1518.
92. Katsuta, K., Nakanishi, H., Shirakawa, K., Yoshida, K., Takagi, K. & Tamura, A. (1995) The neuroprotective effect of the novel noncompetitive NMDA antagonist, FR115427 in focal cerebral ischaemia in rats. J. Cereb. Blood Flow A fetab. 15, 345-348.
93. Keanna, J.F.W., McBurney, R.N., Scherz, M.W., Fischer, J.B., Hamilton, P.N., Smith, S.M., Server, A.C., Finkbeiner, S., Stevens, C.F., Jahr, C. & Weber, E. (1989) Synthesis and characterization of a series of diarylguanidines that are noncompetitive N-methyl-D-aspartate receptor antagonists with neuroprotective properties. Proc. J\ratl Acad. Sei. USA 86, 5631-5635.
94. Kemp,J.A. & Leeson, P.D. (1993) Non-competitive antagonists of excitatory amino acid recep. tors. Trends Pharmacol. Sei. 14, 20-25.
95. Kent, T.A., Eisenberg, H., Quast, M., Anderson, A., Hillman, G. & Campbell, G. (1989) Dextrorphan reduces infarct volume after middle cerebral occlusion in rats: a magnetic resonance imaging and histopathology study. J. Cereb. Blood Flaw Metab. 9, S153.
96. Kirino, T. (1982) Delayed neuronal death in the gerbil hippocampus following ischaemia. Brain Res. 239,57-69.
97. Kochhar, A., Zivin,J.A., Lyden, P.D. & Mazzarella, V. (1988) Glutamate antagonist therapy reduces neurologic deficits produced by focal central nervous system ischaemia. Arch. Neural. 45, 148-153.
98. Koh, J.Y. & Choi, D.W. (1988) Vulnerability of cultured cortical neurones to damage by excitotoxins: differential susceptibility of neurones containing NADPH-diaphorase.J. Neurosci. 8, 2153-2163.
99. KohJ.Y, Goldberg, M.P., Hartley, D.M. & Choi, D.W. (1990) Non-NMDA receptor mediated neurotoxicity in cortical cultures. J. Neurosci. 10, 693-705.
100. Koh, J.Y., Palmer, E. & Cotman, C.W. (1991) Activation of the metabotropic glutamate receptor attenuates N-methyl-D-aspartate neurotoxicity in cortical cultures. Proc. Natl Aead. Sei. USA 88,9431-9435.
101. Kuryatov, A., Laube, B., Betz, H. & Kuhse,J. (1994) Mutational analysis of the glycine-binding site of the NMDA receptor: Structural similarity with bacterial amino acid-binding proteins. jVeuronll, 1291-1300.
102. Kutsuwada, T., Kashiwabuchi, N., Mori, H., Sakimura, K., Kushiya, E., Araki, K., Meguro, H., Masaki, H., Kumanishi, T., Arakawa, M. & Mishina, M. (1992) Molecular diversity of the NMDA receptor channel. Xalure 358, 36-41.
103. Lanier, W.L., Perkins, WJ., Karlsson, B.R., Milde, J.H., Scheithauer, B.W., Shearman, G.T. & Michenfelder,J.D. (1990) The effects of dizocilpine maleate (MK-801), an antagonist of the jV-methyl-D-aspartate receptor, on neurological recovery and histopathology following complete cerebral ischaemia in primates. J. Cereb. Blood Flow Melab. 10, 252-261.
104. Laurie, D.J., PutzkeJ., Zieglänsberger, W, Seeberg, P.H. & Tolle, TR. (1995) The distribution of splice variants of the NMDAR1 subunit mRNA in adult brain. Mol Brain Res. 32, 94-108.
105. Li, H. & Buchan, A.M. (1993) Treatment with an AMPA antagonist 12 hours following severe normothermic forebrain ischaemia prevents CA1 neuronal injury. J. Ctreb. Blood Flow Metab. 13, 933-939.
106. Li, H., Siegel, R.E. & Schwanz, R.D. (1993) Rapid decline of GABAA receptor subunit mRNA expression in hippocampus following transient cerebral ischaemia in gerbil. Hippocampus 3, 527-538.
107. Lo, E.H. & Steinberg, G.K. (1991) Effects ofdetromethorphan on regional cerebral blood flow in focal cerebral ischaemia. J. Cmb. Blood How Metab. 11, 803-809.
108. Lucas, D.R. & NewHouse,J.P. (1957) The toxic effect of sodium L-glutamate on the inner layers of the retina. AMAArch. Opthalmol. 58, 193-201.
109. Lustig, H.S., Ahern, K.B. & Greenberg, D.A. (1992) Antiparkinsonian drugs and in tilro excitotoxicity. Brain Res. 597, 148-150.
110. 2+ influx elicited by glutamate: Role in neuronal death. J. Pharmacol. K\p. Therap. 36, 106-112.
111. Marcoux, EW., Goodrich,J.E. & Dominick, M.A. (1988) Ketamine prevents ischaemic neuronal injury. Brain Res. 452, 329-335.
112. May, P.C. & Robison, P.M. (1993) Cyclothiazide treatment unmasks AMPA excitotoxicity in rat primary hippocampal cultures. J'. Neurochem. 60, 1171-1174.
113. Mayer, M.L. & Westbrook, G.L. (1987) Permeation and block of N-methyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurones. J. Physiol. 394, 510-527.
114. McAuley, M.A. (1995) Rodent models of focal ischaemia. Cerebcascular Brain Metab. Rev. 7, 153-180.
115. McGurk, J.F., Bennett, M.YL. & Zukin, R.S. (1990) Polyamines potentiate responses of N-methyl-D-aspartate receptors expressed in Xenopus oocytes. Proc. Natl Acad. Sei. USA 87, 9971-9974.
116. Meguro, H., Mori, H., Araki, K., Kushiya, E., Kustuwada, T., Yamazaki, M., Kumanishi, T., Arakawa, M., Sakimura, K. & Mishina, M. (1992) Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs. Nature 357, 70-74.
117. Meldrum, B.S. (1988) What are the future prospects for agents decreasing excitatory neurotransmission as anti-epiletic agents? In Frontiers in Excitatory Acid Research (eds Calvalheiro, E.A., Lehmann, J. & Turski, L.), pp. 195-202. Liss, New York.
118. Menniti, F.S., Collins, M.A., Chenard, B.L., Shalaby, I.A. & White, WE (1995) CP-101606, a potent and selective antagonist of forebrain NMDA receptors: in litro neuroprotective activity. Soc. Neurosci. Abstr. 21, 37.1.
119. Minematsu, K., Fisher, M., Li, L., Davis, M.A., Knapp, A.G., Cotter, R.E., McBurney, R.N. & Sotak, C.H. (1993) Effects of a novel NMDA antagonist on experimental stroke rapidly and quantitatively assessed by diffusion weighted MRI. Neural. 43, 397-403.
120. Mishina, M., Mori, H., Araki, K., Kushiya, E., Meguro, H., Kutsuwada, T., Kashiwabuchi, N., Ikeda, K., Nagasawa, M., Yamazaki, M., Masaki, M., Yamajura, T., Morita, T. & Sakimura, K. (1993) Molecular and functional diversity of the NMDA receptor channel. Ann. N.Y.Acad. Sei 707, 136-152.
121. Monyer H., Brunashev, N., Laurie, D.J., Sakmann, B. & Seeberg, P.H. (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12, 529-540.
122. Monyer, H., Sprengel, R., Schoepfer, R., Herb, A., Higuchi, M., Lomeli, H., Burneshev, N., Sakmann, B. & Seeberg, P.H. (1992) Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256, 1217-1221.
123. Moriyoshi, K., Masu, M., Ishii, T., Shiemoto, R., Mizuno, N. & Nakanishi, N. (1991) Molecular cloning and characterization of the rat NMDA receptor. Nature 354, 31-37.
124. Morrisett, R.A., Mott, D.D., Lewis, D.V, Wilson, WA. & Swartzwelder, H.S. (1990) Reduced sensitivity of the JV-methyl-D-aspartate component of synaptic transmission to magnesium in hippocampal slices from immature rats. Dei'. Brain Res. 56, 257-262.
125. Muir, K.W. & Lees, K.R. (1995) Clinical experience with excitatory amino acid antagonist drugs. Stroke 26, 503-513.
126. Nakanishi, N., Azel, R. & Schneider, N. A. (1992) Alternative splicing generates functionally distinct j\-methyl-D-aspartate receptors. Proc. XatlAcad. Sei. USA 89, 8552-8556.
127. Nakanishi, H., Katsuta, K., Ueda, Y, Shiraka\va, K. & Yoshida, K. (1994) Protective effect of FR115427 against hippocampal damage in gerbils. Jpn. J. Pharmacol. 64, 189-193.
128. Newell, D.W., Malouf, A.T. & Franck, J.E. (1990) Glutamate-mediated selective vulnerability to ischaemia is present in organotypic cultures of hippocampus. Neurosci. Letts. 116, 325-330.
129. Nishikawa, T., Kirsch, J.R., Koehler, R.C., Miyabe, M. & Traystman, R J. (1994) Competitive N-methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischaemia in cats. Stroke 25, 2258-2264.
130. Obrenovitch, T.P. & Richards, D.A. (1995) Extracellular neurotransmitter changes in cerebral ischaemia. Cerebvasc. Brain Afelab. Rev. 7, 1-54.
131. O'Hara, PJ., Sheppard, P.O., Thogersen, H., Venezia, D., Haldemann, B.A., McGrane, V, Houamed, K.M., Thomsen, T., Gilbert, C.L. & Mulvihill, E.R. (1993) The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins. Neuron 11, 41-52.
132. Olney,J.W., Ho, O.L. & Rhee, V. (1971) Cytotoxic effects of acidic and sulphur-containing amino acids on the infant mouse central nervous system. Exp. Brain Res. 14, 61-67.
133. Onodera, H., Sato, G. & Kogure, K. (1986) Lesions to the Schaffer collaterals prevent ischaemic death of CA1 pyramidal cells. Neurosd. Letts. 68, 169-174.
134. Ordy, J.M., Volpe, B., Murray, R., Thomas, G., Bialobok, P., Wengenack, T.M. & Dunlap, W. (1992) Pharmacological effects of remacemide and MK-801 on memory and hippocampal CA1 damage in the rat four-vessel occlusion (4-VO) model of global ischaemia. In The Roh ofNeurolransmillers in Brain Injury (eds Globus, M.Y.T. & Dietrich, W.D.), pp. 83-92. Plenum Press, New York.
135. Osborne, N.N. & Quack, G. (1992) Memantine stimulates inositol phosphates production in neurones and nullifies jV-methyl-D-aspartate-induced destruction of retinal neurones. Ncumchan. Int. 21, 329-336.
136. Ozyurt, E., Graham, D.I., Woodruff, G.N. & McCullochJ. (1988) Protective effect of the glutamate antagonist, MK-801, in focal cerebral ischaemia in the cat. J. Cereb. Blood glow Melab. 8, 138-143.
137. Pagnozzi, MJ., Chambers, L.K., Menniti, F.S., Chenard, B.L. & White, WE (1995) CP-101,606, a potent and selective antagonist of forebrain NMDA receptors: in vivo activity. Soc. Murosd. Abslr. 21,439.9.
138. Park, C.K., McBurney, R.N., Holt, WE, Cotter, R.E, McCullochJ., KangJ.K. & Choi, C.R. (1993) The dose-dependency of the antiischacmic efficacy and of the side effects of a novel NMDA antagonist, CNS 1102. J. Cereb. Blood How Metab. 13, S641.
139. Park, C.K., Nehls, D.G., Graham, D.I., Teasdale, G.M. & McCullochJ. (1988a) The glutamate antagonist MK-801 reduces focal ischaemic brain damage in the rat. Ann. Neural. 24, 543-551.
140. Park, C.K., Nehls, D.G., Graham, D.I., Teasdale, G.M. & McCullochJ. (1988b) Focal cerebral ischaemia in the cat: treatment \vith the glutamate antagonist MK-801 after induction of ischaemia. J. Cereb. Blood How Metab. 8, 757-762.
141. Parsons, G.G., Grüner, R., Rozental, J., Millar, J. & Lodge, D. (1993) Patch-clamp studies on the kinetics and selectivity of .N-methyl-D-aspartate receptor antagonism by memantine (1-amino-3,5-dimethyladamantan). Neuropharmacology 32, 1337-1350.
142. Parsons, G.G., Quack, G., Bresink, L, Baran, L., Przegalinski, E., Kostowski, W, Krzascik, P., Hartmann, S. & Danysz, W (1995) Comparison of the potency, kinetics and voltage-dependency of a series of uncompetitive NMDA receptor antagonists in vitro with anticonvulsant and motor impairment activity in vivo. Neuropharmacology 34, 1239-1258.
143. Paschen, W., Schmitt,J., Dux, E. & Djuricic, B. (1995) Temporal analysis of the upregulation of GluRS mRNA editing with age: regional evaluation. Dev. Brain Res. 86, 359-363.
144. Pellegrini-Giampietro, D.E., Pulsinelli, W.A. & Zukin, R.S. (1994) NMDA and non-NMDA receptor gene expression following global ischaemia in rats: Effect of NMDA and nonNMDA receptor antagonists. J. Xeurochem. 62, 1067-1073.
145. Pellegrini-Giampietro, D.E., Zukin, R.S., Bennett, M.VL., Cho, S. & Pulsinelli, W.A. (1992) Switch in glutamate receptor subunit gene expression in CA1 subfield of hippocampus following global ischaemia in rats. Proc.NallAcad. Set. U&l 89, 10499-10503.
146. Ferez-Velazquez, J.L. & Zhang, L. (1994) In titro hypoxia induces expression of the NR2C subunit of NMDA receptor in rat cortex and hippocampus, jf. Neumchrm. 63, 1171-1173.
147. Persson, L., Hardemark, H.G., Bolander, H.G., Hillered, L. & Olsson, Y. (1989) Neurologic and pathologic outcome after middle cerebral artery occlusion in rats. Stroke 20, 641-645.
148. Peterson, C., Neal, J.H. & Cotman, C.W. (1989) Development of N-methyl-D-aspartate excitotoxicity in cultured hippocampal neurones. Dei'. Brain Res. 48, 187-195.
149. Pollard, H., Heron, A., MoreauJ., Ben-Ari, Y. & Khrestchatisky, M. (1993a) Alterations of the GIuR-B AMPA receptor subunit flip/flop expression in kainate-induced epilepsy and ischaemia. Neurosdence 57, 545-554.
150. Pollard, H., Khrestchatisky, M., Moreau, J. & Ben-Ari, Y. (1993b) Transient expression of the NR2C subunit of the NMDA receptor in developing brain. NeuroReport 4, 411-414.
151. Prehn, J.H.M., Dppert, K. & Krieglstein, J. (1995) Are NMDA or AMPA/kainate receptor antagonists more efficacious in the delayed treatment of excitotoxic neuronal injury? Eur.J. Pharmacol. 292, 179-189.
152. Pulsinelli, W.A. & Brierley, J.B. (1979) A new model of bilateral hemisphere ischaemia in the unanesthetized rat. Stroke 10, 267-272.
153. Pulsinelli, W.A., Brierley, J.B. & Plum, F. (1982) Temporal profile of neuronal damage in a model of transient forebrain ischaemia. Ann. Neural. 11, 491-498.
154. Pulsinelli, W.A. & Buchan, A.M. (1990) The NMDA receptor/ion channel: Its importance to in ciro ischaemic injury to selectively vulnerable neurones. In Pharmacology of Cerebral Ischaemia (eds Krieglstein.J. and Oberpichler, H.), pp. 169-175. \Vissenschafdiche Verlagsgesellschaft mbH, Stuttgart.
155. Rader, R.K. & Lanthorn, T.H. (1989) Experimental ischaemia induces a persistent depolarization blocked by decreased calcium and NMDA antagonists. Neurosci. Letts. 99, 125-130.
156. Roberts-LewisJ.M., Marcy, VR., Yonghua, Z., VaughtJ.L., Siman, R. & Lewis, M.E. (1993) Aurintricarboxylic acid protects hippocampal neurones from NMDA- and ischaemiainduced toxicity in tiro.J. Neurochem. 61, 378-381.
157. Rogawski, M.A. (1993) Therapeutic potential of excitatory amino acid antagonists: channel blockers and 2,3-bonzodiazepines. Trends Pharmacol. Sei. 14, 325-331.
158. Rogers, M. & Dani,J.A. (1995) Comparison of quantitative calcium flux through NMDA, ATP and ACh receptor channels. Biophjs.J. 68, 501-508.
159. Roman, R., Bartkowski, H. & Simon, R. (1989) The specific NMDA receptor antagonist AP-7 attenuates focal ischaemic brain injury. Neurosci. Letts. 104, 19-24.
160. Rothman, S.M. & Olney.J.W. (1987) Excitotoxicity and the NMDA receptor. Trends Xeumsci. 10, 299-302.
161. Rothman, S.M., Thurston, J.H. & Hauhart, R.E. (1987) Delayed neurotoxicity of excitatory amino acids in litro. Neuwsci. 22, 471-480.
162. Roussel, S., Pinard, E. & Seylaz,J. (1990) Kyurenate does not reduce infarct size after middle cerebral artery occlusion in spontaneously hypertensive rats. Brain Res. 518, 353-355.
163. Saito, N., Kawai, K. & Nowak, T.S. ( 1995) Re-expression of developmentally regulated MAP2c mRNA after ischaemia: Colocalization with hsp 72 mRNA in vulnerable neurones. J. Cereb. Blood Flow Metab. 15, 205-215.
164. Samples, S.D. & DublinskyJ.M. (1993) Aurintricarboxylic acid protects hippocampal neurones from glutamate excitotoxicity m vitro, J. Neurochem. 61, 382-385.
165. Sather, W., Dieudonné, S., MacDonald, J.F. & Ascher, P. (1992) Activation and desensitization of N-methyl-D-aspartate receptors in nucleated outside-out patches from mouse neurones. J. PlysioL 450,643-672.
166. Sauer, D., Allegrini, P.R., Cosenti, A., Pataki, A., Amacker, H. & Fagg, G.E. (1993) Characterization of the cerebroprotective efficacy of the competitive NMDA receptor antagonist CGP 40116 in a rat model of focal cerebral ischaemia: An in vitro magnetic resonance imaging study. J. Cereb. Blood Flow Metab. 13, 595-602.
167. Sauer, D., Allegrini, P.R. & Fagg, G.E. (1994) The competitive NMDA receptor antagonist CGP 40116 is a potent neuroprotectant in a rat model of focal cerebral ischaemia. J. Neural Transm. 43, 81-89.
168. Sauer, D., Nuglisch, J. & Rossberg, C. (1988) Phencyclidine reduces postischaemic neuronal necrosis in rat hippocampus without changing blood flow. Neurosci. Letts. 91, 327-332.
169. Sauer, D., Weber, E., Luond, G., DaSilva, F. & Allegrini, P.R. (1995) The competitive NMDA antagonist CGP 40116 permanently reduces brain damage after middle cerebral artery occlusion in rats.J. Cereb. Blood Flow Metab. 15, 602-610.
170. Scatton, B., Avenet, P., Benavides,J., Besnard, F., Carter, C., Duverger, D., Graham, D., Langer, A.Z., NowickijJ.P., Santamaria, R. & Schoemaker, H. (1995) Eliprodil, a neuroprotective agent which selectively blocks a subtype of NMDA receptor. In Proceedings of the Symposium on Pre- and Post-Synaptic Modulation of the Glutamate Receptors: Molecular Pharmacology and Therapeutic Implications. San Diego, California, 11 November 1995.
171. Schiff, SJ. & Somjen, G.G. (1987) The effect of graded hypoxia on the hippocampal slice: an in lilro model of the ischaemic penumbra. Stroke 18, 30-37.
172. Schneggenburger, R., Zhou, Z., Konnerth, A. & Neher, E. (1993) Fractional contribution of calcium to the cation current through glutamate receptor channels. Neuron 11, 133-143.
173. Schramm, M., Eimerl, S. & Costa, E. (1990) Serum and depolarizing agents cause acute neurotoxicity in cultured cerebellar granule cells: Role of the glutamate receptor responsive to N-methyl-D-aspartate. Proc. NallAcad. Set. USA 87, 1193-1197.
174. Schurr, A., Payne, R.S., Heine, M.F. & Rigor, B.M. (1995) Hypoxia, excitotoxicity, and neuroprotection in the hippocampal slice preparation. J. Neurosti. Meth. 59, 129-138.
175. Schurr, A., Payne, R.S. & Rigor, B.M. (1993) MK-801 is both an NMDA and a calcium channel blocker in hypoxic hippocampal slices. Soc. jYeurosci. Abstr. 19, 1646.
176. Seeberg, P.H., Burnashev, N., Köhr, G., Kuner, T, Sprengel, R. & Monyer, H. (1995) The NMDA receptor channel: Molecular design of a coincidence detector. Recent Prog. Hormone A. 50, 19-35.
177. Seif el Nasr, M., Peruche, B., Robberg, C., Mennel, H.D. & Krieglstein, J. (1990) Neuroprotective effect of memantine demonstrated in viro and in vitro. Eur.J. Pharmacol. 185, 19-24.
178. Siesjö, B.K. (1981) Cell damage in the brain: a speculative synthesis. J. Cereb. Blood Flow Metab. 1, 155-185.
179. Siesjö, B.K. (1992a) Pathophysiology and treatment of focal cerebral ischaemia. Part I: Pathophysiology. 7 Jfeunsurg. 77, 169-184.
180. Siesjö, B.K. (1992b) Pathophysiology and treatment of focal cerebral ischaemia. Part II: Mechanisms of damage and treatment.J. Neurosurg. 77, 337-354.
181. Simon, R. & Shiraishi, K. (1990) j\-methyl-D-aspartate antagonist reduces stroke size and regional glucose metabolism. Ann. Neural. 27, 606-611.
182. Simon, R.P., SwanJ.H., Griffiths, T. &Meldrum, B.S. (1984) Blockade of N-methyl-D-aspartate receptors may protect against ischaemic damage in the brain. Science 226, 850-852.
183. Small, D.L. & Buchan, A.M. (1996) Mechanisms of cerebral ischaemia: Intracellular cascades and therapeutic interventions. J. Cardiothoracic. Vasc.Anesth. 10, 139-146.
184. Somogyi, R., Wen, X., Dugich-Djordjevic, M.M., Giorgi, O., McKay, R.D. & Barker, J.L. (1995) Induction of embryonic GAD transcripts and nestin following hippocampal injury: Recapitulation of developmental programmes. Soc. Neurosci. Abstr. 21, 426.3.
185. Speilmeyer, W. (1925) Zur pathogenese örtich elektiven gehirnveränderungen. Zeitschrift für die gesamte Neurologie und Psychiatrie 99, 756-776.
186. Steinberg, G.K., Saleh, J. & Kunis, D. (1988a) Delayed treatment with dextromethorphan and dextrorphan reduces cerebral damage after transient focal ischaemia. Neurosn. Letts. 89, 193-197.
187. Steinberg, G.K., George, G.P., DeLaPaz, R., Shibata, D.K. & Gross, T. (1988b) Dextromethorphan protects against cerebral injury following transient focal ischaemia in rabbits. Stroke 19, 1112-1118.
188. Steinberg, G.K., Saleh.J., DeLaPaz, R., Kunis, D. & Zarnegar, S.R. (1989a) Pretreatment with the NMDA antagonist dextrorphan reduces cerebral injury after focal ischaemia in rabbits. Brain Res. 497, 382-386.
189. Steinberg, G.K., SalehJ., Kunis, D., DeLaPaz, R. & Zarnegar, S.R. (1989b) Protective effect of N-methyl-D-aspartate antagonists after focal cerebral ischaemia in rabbits. Stroke 20, 1247-1252.
190. Stern, P., Béhé, P., Schoepfer, R. & Colquhoun, D. (1992) Single channel conductances of NMDA receptor expressed from cloned cDNAs: comparison with native receptors. Proc. Roy. Soc.(Lond.) 250, 271-277.
191. Stern-Bach, Y, Bettler, B., Hartley, M., Sheppard, P.O., O'Hara, PJ. & Heinemann, S. (1994) Agonist selectivity of glutamate receptors is specified by two domains structurally related to bacterial amino acid-binding proteins. Neuron 13, 1345-1357.
192. Stoppini, L., Buchs, P.A. & Muller, D. (1991) A simple method for organotypic cultures of nervous tissue. J. Neurosci. Meth. 37, 173-182.
193. Strasser, U. & Fischer, G. (1995) Quantitative measurement of neuronal degeneration in organotypic cultures after combined oxygen/glucose deprivation. J. Neurosci. Meth. 57, 177-186.
194. Subramaniam, S., Donevan, S.D. & Rogawski, M.A. (1996) Block of the N-methyl-D-aspartate receptor by remacemide and its (/-glycine metabolite. J. Pliarmacol. Exp. Therap. 276, 161-168.
195. Sugihara, H., Moriyoshi, K., Ishii, T., Masu, M. & Nakanishi, S. (1992) Structures and properties of seven isoforms of the NMDA receptor generated by alternative splicing. Biochem. Biophys. Res. Commun. 185, 826-832.
196. Sugimoto, A., Takeda, A., Kogure, K. & Onodera, H. (1994) NMDA receptor (NMDAR1) expression in the rat after forebrain ischaemia. Neurosci. Letts. 170, 39-42.
197. Swan.J.H., Evans, M.C. & Meldrum, B.S. (1988) Long-term development of selective neuronal loss and the mechanism of protection by 2-amino-7-phosphonoheptanoate in a rat model of incomplete forebrain ischaemia. J. Cereb. Blood Flow hletab. 8, 64-78.
198. Swan, J.H. & Meldrum, B.S. (1990) Protection by NMDA antagonists against selective cell loss following transient ischaemia. J. Cereb. Blood Flow A fetab. 10, 343-351.
199. Takizawa, S., Hogan, M. & Hakim, A.M. (1991) The effects of a competitive NMDA receptor antagonist (CGS-19755) on cerebral blood flow and pH in focal ischaemia.J. Cereb. Blood Flow Melab. 11,786-793.
200. Tarnawa, I., Farkas, S., Berzsenyi, P., Pataki, A. & Andrasi, F. (1989) Electrophysiological studies with a 2,3-benzodiazepine muscle relaxant: GYKI 52466. Eur. J. Pliarmacol. 167, 193-199.
201. Torp, R., Haug, F.M., Tonder, N., Zimmer, J. & Ottersen, O.P. (1992) Neuroactive amino acids in organotypic slice cultures of rat hippocampus: an immunocytochemical study of the distribution of GABA, glutamate, glutamine and taurine. Neuroscience. 46, 807-823.
202. Toulmond, S., Serrano, A., Benavides, J. & Scatton, B. (1993) Prevention by eliprodil (SL 82.0715) of traumatic brain damage in the rat. Existence of a large (18 h) therapeutic window. Brain Res. 620, 32-41.
203. Traynelis, S.F., Hartley, M. & Heinemann, S.F. (1995) Control of proton sensitivity of the NMDA receptor RNA splicing and polyamines. Science 268, 873-876.
204. 2+-dependent non-NMDA receptor-mediated synaptic currents in ischaemic CA1 hippocampal neurones. J. Neurophjsiol. 71, 1190-1196.
205. Villarroel, A., Burnashev, N. & Sakmann, B. (1995) Dimensions of the narrow portion of a recombinant NMDA receptor channel. Biopfys.J. 68, 866-875.
206. von Lubitz, D.K.J.E., Lin, R.C.S., McKenzie, R J., Devlin, T.M., McCabe, R.T. & Skolnick, P. (1992) A novel treatment of global cerebral ischaemia with a glycine partial agonist. Eur.J. Pharmacol. 219, 153-158.
207. Vornav,JJ. & Coyle, J.T. (1991) Enhancement of NMDA receptor-mediated neurotoxicity in the hippocampal slice by depolarization and ischaemia. Brain Res. 555, 99-106.
208. Vornov, J J., Tasker, R.C. & Coyle, J.T. ( 1994) Delayed protection by MK-801 and tetrodotoxin in a rat organotypic hippocampal culture model of ischaemia. Stroke 25, 457-465.
209. VornovJJ., Tasker, R.C. & Coyle.J.T. (1991) Direct observation of the agonist-specific regional vulnerability to glutamate, NMDA and kainate neurotoxicity in organotypic hippocampal cultures. Exp. Neural. 114, 11-22
210. Wafford, K.A., Bain, CJ., Bourdelles, B.L., \Vhiting, PJ. & Kemp,J.A. (1993) Preferential coassembly of recombinant NMDA receptors composed of three different subunits. NeuroReport 4,1347-1349.
211. Wahlestedt, C., Golanov, E., Yamamoto, S., Yee, E Ericson, H., Yoo, H., Inturrisi, C.E. & Reis, DJ. (1993) Antisense oligodeoxynucleotides to NMDA-R1 receptor channel protect cortical neurones from excitotoxicity and reduce focal ischaemic infarctions. Nature 363, 260-263.
212. Wallis, R.A., Panizzon, K.L., Fairchild, M.D. & Wasterlain, G.G. (1992) Protective effects of felbamate against hypoxia in the rat hippocampal slice. Stroke 23, 547-551.
213. Warner, D.S., Martin, H., Ludwig, P., McAllister, A., Keana, J.EW. & Weber, E. (1995) In vivo models of cerebral ischaemia: effects of parenterally administered NMDA receptor glycine site antagonists. J. Cmb. Blood Flow Me lab. 15, 188-196.
214. Warner, M.A., Neill, K.H., Nadler, J.V. & Grain, BJ. (1991) Regionally selective effects of NMDA receptor antagonists against ischaemia brain damage in the gerbil.J'. Cmb. Blood Flow Metab. 11, 600-610.
215. Wasterlain, G.G., Adams, L.M., Hattori, H. & Schwartz, P.H. (1992) Felbamate reduces hypoxicischaemic brain damage in vim. Eur.J. Pharmacol. 212, 275-278.
216. Weller, M., Finiels-Marlier, F. & Paul, S.M. (1993) NMDA receptor-mediated glutamate toxicity of cultured cerebellar, cortical and mesencephalic neurones: neuroprotective properties of amantadine and memantine. Brain Res. 613, 143-148.
217. Westbrook, G.L. & Mayer, M.L. (1987) Micromolar concentrations of Zn2+ antagonize NMDA and GABA responses of hippocampal neurones. Nature 328, 640-643.
218. White, WE, Ducat, M.F., Chenard, B.L, Butler, T.W. & Ronau, R.T. (1995) CP-101,606, a potent and selective antagonist of forebrain NMDA receptors: Binding to a novel recognition site. Soc. Neurosci. Abstr. 21, 439.7.
219. Wieloch, T., Gustafsson, I. & Westerberg, E. (1988) Effects of the noncompetitive NMDA receptor antagonist MK-801 on ischaemic and hypoglycémie brain damage. In Frontiers in Excitatory Amino Acid Research, Vol. 46, Neurology and Neurobiology (eds Cavalheiro, E.A., LehmannJ. & Turski, L.) pp. 715-722. Liss, New York.
220. Wieloch, T., Lindvall, O., Blomquist, P. & Gage, F.H. (1985) Evidence for amelioration of ischaemic neuronal damage in the hippocampal formation by lesions of the perforant path. Neural. Res. 7, 24-26.
221. Williams, K. (1993) Ifenprodil discriminates subtypes of the N-methyl-D-aspartate receptor: selectivity and mechanisms at recombinant heteromeric receptors. Mol. Pharmacol. 44, 851-859.
222. Williams, K., Zappia, A.M., Pritchett, D.B., Shen, Y.M. & MolinofT, P.B. (1994) Sensitivity of the N-methyl-D-aspartate receptor to polyamines is controlled by NR2 subunits. Mol. Pharmacol. 45, 803-809.
223. Xue, D., Huang, Z.G., Barnes, K., Lesiuk, HJ., Smith, K.E. & Buchan, A.M. (1994) Delayed treatment with AMPA, but not NMDA antagonists reduces neocortical infarction. J. Cereb. Blood Flow Metab. 14, 251-261.
224. Yamazaki, M., Mori, H., Araki, K., Mori, KJ. & Mishina, M. (1992) Cloning, expression and modulation of a mouse NMDA receptor subunit. FEDS Letts. 300, 39-45.
225. Zeevalk, G.D., Schoepp, D. & Nicklas, WJ. (1993) Aurintricarboxylic acid prevent NMDAmediated excitotoxicity: evidence for its action as an NMDA receptor antagonists. J. Kanadiern. 61, 386-389.
226. Zeevalk, G.D., Schoepp, D. & Nicklas, WJ. (1995) Excitotoxicity at both NMDA and non-NMDA glutamate receptors is antagonized by aurintricarboxylic acid: evidence for differing mechanisms of action. J. Neurochem. 64, 1749-1758.
227. Zhang, L., Miu, P. & Eubanks, J.H. (1995) NMDA channel activities in rat CA1 hippocampal neurones following a brief hypoxic-hypoglycaemic challenge in brain slices. Soc. Neurosci. Abstr. 21,392.1.
228. Zorumski, C.F., Thio, L.L., Clark, G.D. & Clifford, D.B. (1990) Blockade of desensitization aug-ments quisqualate excitotoxicity in hippocampal neurones. Neuron 5, 61-66.
229. Zukin, R.S. & Bennett, M.V.L. (1995) Alternatively spliced isoforms of the NMDAR1 receptor subunit. Trends Pharmacol. Sd. 18, 306-313.